The Journal of Cell Biology, Vol 118, 929-936, Copyright © 1992 by The Rockefeller University Press

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Enteric defensins: antibiotic peptide components of intestinal host defense

ME Selsted, SI Miller, AH Henschen and AJ Ouellette
Department of Pathology, College of Medicine, University of California, Irvine 92717.

Five intestinal defensins, termed cryptdins 1-5, have been purified from mouse small bowel, sequenced, and localized to the epithelium by immunohistochemistry. Although identified as members of the defensin peptide family by peptide sequencing, enteric defensins are novel in that four cryptdins have amino termini which are three to six residues longer than those of leukocyte-derived defensins. A fifth cryptdin is the first defensin to diverge from the previously invariant spacing of cysteines in the peptide structure. The most abundant enteric defensin, cryptdin-1, had antimicrobial activity against an attenuated phoP mutant of Salmonella typhimurium but was not active against the virulent wild-type parent. Immunohistochemical localization demonstrated that cryptdin-1, and probably cryptdins 2 and 3, occur exclusively in Paneth cells, where the peptides appear to be associated with cytoplasmic granules. Biochemical and immunologic analysis of the luminal contents of the small intestine suggest that cryptdin peptides are secreted into the lumen, similar to Paneth cell secretion of lysozyme. The presence of several enteric defensins in the intestinal epithelium, evidence of their presence in the lumen, and the antibacterial activity of cryptdin-1 suggest that these peptides contribute to the antimicrobial barrier function of the small bowel mucosa.
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• Amann, J. M., Chyla, B. J. I., Ellis, T. C., Martinez, A., Moore, A. C., Franklin, J. L., McGhee, L., Meyers, S., Ohm, J. E., Luce, K. S., Ouelette, A. J., Washington, M. K., Thompson, M. A., King, D., Gautam, S., Coffey, R. J., Whitehead, R. H., Hiebert, S. W. (2005). Mtgr1 Is a Transcriptional Corepressor That Is Required for Maintenance of the Secretory Cell Lineage in the Small Intestine. Mol. Cell. Biol. 25: 9576-9585 [Abstract] [Full Text]  
• Bevins, C. L. (2005). Events at the Host-Microbial Interface of the Gastrointestinal Tract V. Paneth cell {alpha}-defensins in intestinal host defense. Am. J. Physiol. Gastrointest. Liver Physiol. 289: G173-G176 [Abstract] [Full Text]  
• Tanabe, H., Ouellette, A. J., Cocco, M. J., Robinson, W. E. Jr. (2004). Differential Effects on Human Immunodeficiency Virus Type 1 Replication by {alpha}-Defensins with Comparable Bactericidal Activities. J. Virol. 78: 11622-11631 [Abstract] [Full Text]  
• Maemoto, A., Qu, X., Rosengren, K. J., Tanabe, H., Henschen-Edman, A., Craik, D. J., Ouellette, A. J. (2004). Functional Analysis of the {alpha}-Defensin Disulfide Array in Mouse Cryptdin-4. J. Biol. Chem. 279: 44188-44196 [Abstract] [Full Text]  
• Tanabe, H., Qu, X., Weeks, C. S., Cummings, J. E., Kolusheva, S., Walsh, K. B., Jelinek, R., Vanderlick, T. K., Selsted, M. E., Ouellette, A. J. (2004). Structure-Activity Determinants in Paneth Cell {alpha}-Defensins: LOSS-OF-FUNCTION IN MOUSE CRYPTDIN-4 BY CHARGE-REVERSAL AT ARGININE RESIDUE POSITIONS. J. Biol. Chem. 279: 11976-11983 [Abstract] [Full Text]  
• Tanabe, H., Yuan, J., Zaragoza, M. M., Dandekar, S., Henschen-Edman, A., Selsted, M. E., Ouellette, A. J. (2004). Paneth Cell {alpha}-Defensins from Rhesus Macaque Small Intestine. Infect. Immun. 72: 1470-1478 [Abstract] [Full Text]  
• Hsia, N., Cornwall, G. A. (2004). DNA Microarray Analysis of Region-Specific Gene Expression in the Mouse Epididymis. Biol. Reprod. 70: 448-457 [Abstract] [Full Text]  
• Cunliffe, R. N., Mahida, Y. R. (2004). Expression and regulation of antimicrobial peptides in the gastrointestinal tract. J. Leukoc. Biol. 75: 49-58 [Abstract] [Full Text]  
• Wehkamp, J, Schmidt, K, Herrlinger, K R, Baxmann, S, Behling, S, Wohlschlager, C, Feller, A C, Stange, E F, Fellermann, K (2003). Defensin pattern in chronic gastritis: HBD-2 is differentially expressed with respect to Helicobacter pylori status. J. Clin. Pathol. 56: 352-357 [Abstract] [Full Text]  
• Satchell, D. P., Sheynis, T., Shirafuji, Y., Kolusheva, S., Ouellette, A. J., Jelinek, R. (2003). Interactions of Mouse Paneth Cell alpha -Defensins and alpha -Defensin Precursors with Membranes. PROSEGMENT INHIBITION OF PEPTIDE ASSOCIATION WITH BIOMIMETIC MEMBRANES. J. Biol. Chem. 278: 13838-13846 [Abstract] [Full Text]  
• Salzman, N. H., Chou, M. M., de Jong, H., Liu, L., Porter, E. M., Paterson, Y. (2003). Enteric Salmonella Infection Inhibits Paneth Cell Antimicrobial Peptide Expression. Infect. Immun. 71: 1109-1115 [Abstract] [Full Text]  
• Shirafuji, Y., Tanabe, H., Satchell, D. P., Henschen-Edman, A., Wilson, C. L., Ouellette, A. J. (2003). Structural Determinants of Procryptdin Recognition and Cleavage by Matrix Metalloproteinase-7. J. Biol. Chem. 278: 7910-7919 [Abstract] [Full Text]  
• Bajaj-Elliott, M (2003). Trypsin and host defence: a new role for an old enzyme. Gut 52: 166-167 [Full Text]  
• Saarinen, M., Ekman, P., Ikeda, M., Virtala, M., Gronberg, A., Yu, D. T. Y., Arvilommi, H., Granfors, K. (2002). Invasion of Salmonella into human intestinal epithelial cells is modulated by HLA-B27. Rheumatology (Oxford) 41: 651-657 [Abstract] [Full Text]  
• Ayabe, T., Satchell, D. P., Pesendorfer, P., Tanabe, H., Wilson, C. L., Hagen, S. J., Ouellette, A. J. (2002). Activation of Paneth Cell alpha -Defensins in Mouse Small Intestine. J. Biol. Chem. 277: 5219-5228 [Abstract] [Full Text]  
• SAARINEN, M., EKMAN, P., HE, Q., IKEDA, M., VIRTALA, M., YU, D. T. Y., ARVILOMMI, H., GRANFORS, K. (2002). Elimination of Salmonella enterica serotype Enteritidis in intestinal epithelial cells by mechanisms other than nitric oxide. J Med Microbiol 51: 13-19 [Abstract] [Full Text]  
• Vizioli, J., Bulet, P., Hoffmann, J. A., Kafatos, F. C., Muller, H.-M., Dimopoulos, G. (2001). Gambicin: A novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae. Proc. Natl. Acad. Sci. USA 10.1073/pnas.221466798v1 [Abstract] [Full Text]  
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• Cunliffe, R N, Rose, F R A J, Keyte, J, Abberley, L, Chan, W C, Mahida, Y R (2001). Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease. Gut 48: 176-185 [Abstract] [Full Text]  
• Merlin, D., Yue, G., Lencer, W. I., Selsted, M. E., Madara, J. L. (2001). Cryptdin-3 induces novel apical conductance(s) in Cl{-} secretory, including cystic fibrosis, epithelia. Am. J. Physiol. Cell Physiol. 280: C296-C302 [Abstract] [Full Text]  
• Haynes, R. J., McElveen, J. E., Dua, H. S., Tighe, P. J., Liversidge, J. (2000). Expression of Human Beta-Defensins in Intraocular Tissues. IOVS 41: 3026-3031 [Abstract] [Full Text]  
• CUNLIFFE, R N, MAHIDA, Y R (2000). Antimicrobial peptides in innate intestinal host defence. Gut 47: 16-17 [Full Text]  
• Yu, Q., Lehrer, R. I., Tam, J. P. (2000). Engineered Salt-insensitive alpha -Defensins with End-to-end Circularized Structures. J. Biol. Chem. 275: 3943-3949 [Abstract] [Full Text]  
• Stappenbeck, T., Gordon, J. (2000). Rac1 mutations produce aberrant epithelial differentiation in the developing and adult mouse small intestine. Development 127: 2629-2642 [Abstract]  
• Ouellette, A. J., Darmoul, D., Tran, D., Huttner, K. M., Yuan, J., Selsted, M. E. (1999). Peptide Localization and Gene Structure of Cryptdin 4, a Differentially Expressed Mouse Paneth Cell alpha -Defensin. Infect. Immun. 67: 6643-6651 [Abstract] [Full Text]  
• BEVINS, C L, MARTIN-PORTER, E, GANZ, T (1999). Defensins and innate host defence of the gastrointestinal tract. Gut 45: 911-915 [Full Text]  
• Castle, M., Nazarian, A., Yi, S. S., Tempst, P. (1999). Lethal Effects of Apidaecin on Escherichia coli Involve Sequential Molecular Interactions with Diverse Targets. J. Biol. Chem. 274: 32555-32564 [Abstract] [Full Text]  
• Wilson, C. L., Ouellette, A. J., Satchell, D. P., Ayabe, T., López-Boado, Y. S., Stratman, J. L., Hultgren, S. J., Matrisian, L. M., Parks, W. C. (1999). Regulation of Intestinal -Defensin Activation by the Metalloproteinase Matrilysin in Innate Host Defense. Science 286: 113-117 [Abstract] [Full Text]  
• Yount, N. Y., Yuan, J., Tarver, A., Castro, T., Diamond, G., Tran, P. A., Levy, J. N., McCullough, C., Cullor, J. S., Bevins, C. L., Selsted, M. E. (1999). Cloning and Expression of Bovine Neutrophil beta -Defensins. BIOSYNTHETIC PROFILE DURING NEUTROPHILIC MATURATION AND LOCALIZATION OF MATURE PEPTIDE TO NOVEL CYTOPLASMIC DENSE GRANULES. J. Biol. Chem. 274: 26249-26258 [Abstract] [Full Text]  
• Condon, M. R., Viera, A., D'Alessio, M., Diamond, G. (1999). Induction of a Rat Enteric Defensin Gene by Hemorrhagic Shock. Infect. Immun. 67: 4787-4793 [Abstract] [Full Text]  
• Hecht, G. (1999). Innate mechanisms of epithelial host defense: spotlight on intestine. Am. J. Physiol. Cell Physiol. 277: C351-C358 [Abstract] [Full Text]  
• Ouellette, A. J. (1999). IV. Paneth cell antimicrobial peptides and the biology of the mucosal barrier. Am. J. Physiol. Gastrointest. Liver Physiol. 277: G257-G261 [Abstract] [Full Text]  
• Haynes, R. J., Tighe, P. J., Dua, H. S. (1999). Antimicrobial defensin peptides of the human ocular surface. Br J Ophthalmol 83: 737-741 [Abstract] [Full Text]  
• Shirafuji, Y., Oono, T., Kanzaki, H., Hirakawa, S., Arata, J. (1999). Detection of Cryptdin in Mouse Skin. CVI 6: 336-340 [Abstract] [Full Text]  
• Wice, B. M., Gordon, J. I. (1998). Forced Expression of Id-1 in the Adult Mouse Small Intestinal Epithelium Is Associated with Development of Adenomas. J. Biol. Chem. 273: 25310-25319 [Abstract] [Full Text]  
• Shimada, O., Ishikawa, H., Tosaka–Shimada, H., Yasuda, T., Kishi, K., Suzuki, S. (1998). Detection of Deoxyribonuclease I Along the Secretory Pathway in Paneth Cells of Human Small Intestine. J. Histochem. Cytochem. 46: 833-840 [Abstract] [Full Text]  
• Rose, F. R. A. J., Bailey, K., Keyte, J. W., Chan, W. C., Greenwood, D., Mahida, Y. R. (1998). Potential Role of Epithelial Cell-Derived Histone H1 Proteins in Innate Antimicrobial Defense in the Human Gastrointestinal Tract. Infect. Immun. 66: 3255-3263 [Abstract] [Full Text]  
• Tarver, A. P., Clark, D. P., Diamond, G., Russell, J. P., Erdjument-Bromage, H., Tempst, P., Cohen, K. S., Jones, D. E., Sweeney, R. W., Wines, M., Hwang, S., Bevins, C. L. (1998). Enteric beta -Defensin: Molecular Cloning and Characterization of a Gene with Inducible Intestinal Epithelial Cell Expression Associated with Cryptosporidium parvum Infection. Infect. Immun. 66: 1045-1056 [Abstract] [Full Text]  
• Yan, L., Adams, M. E. (1998). Lycotoxins, Antimicrobial Peptides from Venom of the Wolf Spider Lycosa carolinensis. J. Biol. Chem. 273: 2059-2066 [Abstract] [Full Text]  
• McCormick, B. A., Parkos, C. A., Colgan, S. P., Carnes, D. K., Madara, J. L. (1998). Apical Secretion of a Pathogen-Elicited Epithelial Chemoattractant Activity in Response to Surface Colonization of Intestinal Epithelia by Salmonella typhimurium. J. Immunol. 160: 455-466 [Abstract] [Full Text]  
• Lehane, M. J., Wu, D., Lehane, S. M. (1997). Midgut-specific immune molecules are produced by the blood-sucking insect calcitrans. Proc. Natl. Acad. Sci. USA 94: 11502-11507 [Abstract] [Full Text]  
• Garabedian, E. M., Roberts, L. J. J., McNevin, M. S., Gordon, J. I. (1997). Examining the Role of Paneth Cells in the Small Intestine by Lineage Ablation in Transgenic Mice. J. Biol. Chem. 272: 23729-23740 [Abstract] [Full Text]  
• Lencer, W. I., Cheung, G., Strohmeier, G. R., Currie, M. G., Ouellette, A. J., Selsted, M. E., Madara, J. L. (1997). Induction of epithelial chloride secretion by channel-forming cryptdins 2 and 3. Proc. Natl. Acad. Sci. USA 94: 8585-8589 [Abstract] [Full Text]  
• Stolzenberg, E. D., Anderson, G. M., Ackermann, M. R., Whitlock, R. H., Zasloff, M. (1997). Epithelial antibiotic induced in states of disease. Proc. Natl. Acad. Sci. USA 94: 8686-8690 [Abstract] [Full Text]  
• Frohm, M., Agerberth, B., Ahangari, G., Stahle-Backdahl, M., Liden, S., Wigzell, H., Gudmundsson, G. H. (1997). The Expression of the Gene Coding for the Antibacterial Peptide LL-37 Is Induced in Human Keratinocytes during Inflammatory Disorders. J. Biol. Chem. 272: 15258-15263 [Abstract] [Full Text]  
• Cole, A. M., Weis, P., Diamond, G. (1997). Isolation and Characterization of Pleurocidin, an Antimicrobial Peptide in the Skin Secretions of Winter Flounder. J. Biol. Chem. 272: 12008-12013 [Abstract] [Full Text]  
• Bry, L., Falk, P. G., Midtvedt, T., Gordon, J. I. (1996). A Model of Host-Microbial Interactions in an Open Mammalian Ecosystem. Science 273: 1380-1383 [Abstract]  
• Bateman, A., MacLeod, R. J., Lembessis, P., Hu, J., Esch, F., Solomon, S. (1996). The Isolation and Characterization of a Novel Corticostatin/Defensin-like Peptide from the Kidney. J. Biol. Chem. 271: 10654-10659 [Abstract] [Full Text]  
• Andersson, M., Holmgren, A., Spyrou, G. (1996). NK-lysin, a Disulfide-containing Effector Peptide of T-lymphocytes, Is Reduced and Inactivated by Human Thioredoxin Reductase. J. Biol. Chem. 271: 10116-10120 [Abstract] [Full Text]  
• Mallow, E. B., Harris, A., Salzman, N., Russell, J. P., DeBerardinis, R. J., Ruchelli, E., Bevins, C. L. (1996). Human Enteric Defensins. J. Biol. Chem. 271: 4038-4045 [Abstract] [Full Text]  
• Ouellette, A. J., Satchell, D. P., Hsieh, M. M., Hagen, S. J., Selsted, M. E. (2000). Characterization of Luminal Paneth Cell alpha -Defensins in Mouse Small Intestine. ATTENUATED ANTIMICROBIAL ACTIVITIES OF PEPTIDES WITH TRUNCATED AMINO TERMINI. J. Biol. Chem. 275: 33969-33973 [Abstract] [Full Text]  
• Putsep, K., Axelsson, L.-G., Boman, A., Midtvedt, T., Normark, S., Boman, H. G., Andersson, M. (2000). Germ-free and Colonized Mice Generate the Same Products from Enteric Prodefensins. J. Biol. Chem. 275: 40478-40482 [Abstract] [Full Text]  
• Vizioli, J., Bulet, P., Hoffmann, J. A., Kafatos, F. C., Muller, H.-M., Dimopoulos, G. (2001). Gambicin: A novel immune responsive antimicrobial peptide from the malaria vector Anopheles gambiae. Proc. Natl. Acad. Sci. USA 98: 12630-12635 [Abstract] [Full Text]  
• Yue, G., Merlin, D., Selsted, M. E., Lencer, W. I., Madara, J. L., Eaton, D. C. (2002). Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells. Am. J. Physiol. Gastrointest. Liver Physiol. 282: G757-G765 [Abstract] [Full Text]  

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